BMP signalling facilitates transit amplification in the developing chick and human cerebellum

Author:

Rook Victoria12ORCID,Haldipur Parthiv34ORCID,Millen Kathleen J3ORCID,Butts Thomas5ORCID,Wingate Richard J2ORCID

Affiliation:

1. School of Biological and Chemical Sciences, Queen Mary University of London

2. MRC Centre for Neurodevelopmental Disorders, King’s College London

3. Centre for Integrative Brain Research, Seattle Children’s Research Institute, University of Washington

4. Great Ormond Street Institute of Child Health, University College London

5. School of Medicine, University of Sunderland

Abstract

The external granule layer (EGL) is a transient proliferative layer that gives rise to cerebellar granule cell neurons. Extensive EGL proliferation characterises the foliated structure of amniote cerebella, but the factors that regulate EGL formation, amplification within it, and differentiation from it, are incompletely understood. Here, we characterise bone morphogenic protein (BMP) signalling during cerebellar development in chick and human and show that while in chick BMP signalling correlates with external granule layer formation, in humans BMP signalling is maintained throughout the external granule layer after the onset of foliation. We also show via Immunohistochemical labelling of phosphorylated Smad1/5/9 the comparative spatiotemporal activity of BMP signalling in chick and human. Using in-ovo electroporation in chick, we demonstrate that BMP signalling is necessary for subpial migration of granule cell precursors and hence the formation of the external granule layer (EGL) prior to transit amplification. However, altering BMP signalling does not block the formation of mature granule neurons but significantly disrupts that pattern of morphological transitions that accompany transit amplification. Our results elucidate two key, temporally distinct roles for BMP signalling in vivo in organising first the assembly of the EGL from the rhombic lip and subsequently the tempo of granule neuron production within the EGL.

Publisher

eLife Sciences Publications, Ltd

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